While polyomaviruses can induce cell transformation in cell culture and in animal models, their role in causing human cancers has been controversial. A new member of this family, named Merkel cell polyomavirus (MCV) was reported to be a potential etiological agent for the rare Merkel cell carcinoma (MCC) in early 2008. Subsequently, high incidence of MCV in MCC was confirmed with samples from North America, Europe and Australia. MCV appears to be present in 8-16% of control samples with very low copy number in various tissues of gastrointestinal tract and skin, compared to 80% of Merkel cell cancer samples. Such phenomenon is also documented in other known human oncogenic viruses. In addition, a number of oncogenic viruses cause more than one type of cancer. For example, herpesvirus-8 (HHV-8)/Kaposi's sarcoma herpesvirus (KSHV) causes Kaposi's sarcoma, lymphoma and other diseases. Interestingly, Merkel cell carcinoma and Kaposi's sarcoma share a similar epidemiological profile. Therefore, we hypothesize that MCV is also associated with other cancers in additional to the Merkel cell tumor. We are also interested in finding if the other known and unknown polyomaviruses are also associated with cancer development. To achieve these goals, we will create a variety of reagents and assays to determine the involvement of human polyomaviruses, particularly MCV, in different types of cancers. Our specific aims are 1. Developing MCV immunoassays for seroepidimiological studies and MCV-specific antibodies for cancer immunohistochemical analyses. 2. Identifying polyomaviruses in cancer with a comprehensive array-based assay;3. Using a case-control design, establish preliminary seroepidemiologic evidence for or against MCV as a causal agent in a spectrum of cancers. Once establishing the etiological role of the virus, we will potentially use this virus as a diagnostic and prognostic biomarker and as a potential therapeutic target. These longer term goals have been successfully demonstrated in other oncogenic viruses, such as hepatitis B virus and human papillomaviruses. PUBLIC HEALTH RELEVANCE: Polyomavirus- Associated Human Cancers A recently discovered virus, named Merkel cell polyomavirus (MCV), may become the 7th bona fide human cancer-causing virus. This study aims to investigate the association of this virus and various types of cancer and to evaluate the use of this virus as a diagnostic and prognostic marker. A potential long term goal is to develop a vaccine targeting MCV for cancer prevention.